Article

Human RECQ helicases: Roles in DNA metabolism, mutagenesis and cancer biology

Department of Pathology, University of Washington, Seattle, WA 98195-7705, USA.
Seminars in Cancer Biology (Impact Factor: 9.33). 10/2010; 20(5):329-39. DOI: 10.1016/j.semcancer.2010.10.002
Source: PubMed

ABSTRACT Helicases use the energy of ATP hydrolysis to separate double-stranded nucleic acids to facilitate essential processes such as replication, recombination, transcription and repair. This article focuses on the human RECQ helicase gene and protein family. Loss of function of three different members has been shown to cause Bloom syndrome (BS), Werner syndrome (WS) and Rothmund-Thomson syndrome (RTS). This article outlines clinical and cellular features of these cancer predisposition syndromes, and discusses their pathogenesis in light of our understanding of RECQ helicase biochemical activities and in vivo functions. I also discuss the emerging role for RECQ helicases as predictors of disease risk and the response to therapy.

0 Followers
 · 
142 Views
 · 
2 Downloads
  • Source
    • "RecQ helicases are a family of DNA strand-separating enzymes conserved from bacteria to humans that play a crucial role in the maintenance of genome stability [1]. Bacteria have only one RecQ homolog, whereas higher eukaryotic organisms express multiple homologs of RecQ enzymes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: RecQ DNA helicases are key enzymes in the maintenance of genome integrity, and they have functions in DNA replication, recombination, and repair. In contrast to most RecQs, RecQ from Deinococcus radiodurans (DrRecQ) possesses an unusual domain architecture that is crucial for its remarkable ability to repair DNA. Here, we determined the crystal structures of the DrRecQ helicase catalytic core and its ADP-bound form, revealing interdomain flexibility in its first RecA-like and winged-helix (WH) domains. Additionally, the WH domain of DrRecQ is positioned in a different orientation from that of the E. coli RecQ (EcRecQ). These results suggest that the orientation of the protein during DNA-binding is significantly different when comparing DrRecQ and EcRecQ.
    BioMed Research International 08/2014; 2014:342725. DOI:10.1155/2014/342725 · 2.71 Impact Factor
  • Source
    • "This protein displays functional interaction with BRCA1 in breast and ovary cancer suppression and DNA repair [47] [48] and, in turn, BRCA1 is known to be involved in OS-related mechanisms [49]. Moreover, FANCJ/BACH1/BRIP1 competes with Nrf2, leading to negative regulation of the antioxidant-response element-mediated NAD(P)H:quinone oxidoreductase 1 gene expression and induction in response to antioxidants [50], and features a helicase activity and an ATPase activity, a twofold activity that is recognized for other RECQ helicases that are associated with ATPase activity [51]. Furthermore, FANCJ/ BACH1/BRIP1 regulates heme oxygenase-1 [52] [53], senses oxidative DNA damage, and is stimulated by replication protein A to unwind the damaged DNA substrate in a strand-specific manner [54]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Fanconi anaemia (FA) is a rare genetic disease associated to deficiencies in DNA repair pathways. A body of literature points to a prooxidant state in FA patients, along with the evidence for oxidative stress (OS) in FA phenotype reported by in vitro, molecular and animal studies. A highlight arises from the detection of mitochondrial dysfunction (MDF) in FA cell lines of complementation groups A, C, D2 and G. As yet lacking, in vivo studies should focus on FA-associated MDF that may help understanding the mitochondrial basis of OS detected in cells and body fluids from FA patients. Beyond the in vitro and animal database, the available analytical devices may prompt the direct observation of metabolic and mitochondrial alterations in FA patients. These studies should evaluate a set of MDF-related endpoints, to be related with OS endpoints. The working hypothesis is raised that, parallel to OS, nitrosative stress might be another, so far unexplored hallmark of FA phenotype. The expected results may shed light into FA pathogenesis and might provide the grounds for pilot chemoprevention trials using mitochondrial nutrients.
    Free Radical Biology and Medicine 01/2013; 58. DOI:10.1016/j.freeradbiomed.2013.01.015 · 5.71 Impact Factor
  • Source
    • "This protein displays functional interaction with BRCA1 in breast and ovary cancer suppression and DNA repair [47] [48] and, in turn, BRCA1 is known to be involved in OS-related mechanisms [49]. Moreover, FANCJ/BACH1/BRIP1 competes with Nrf2, leading to negative regulation of the antioxidant-response element-mediated NAD(P)H:quinone oxidoreductase 1 gene expression and induction in response to antioxidants [50], and features a helicase activity and an ATPase activity, a twofold activity that is recognized for other RECQ helicases that are associated with ATPase activity [51]. Furthermore, FANCJ/ BACH1/BRIP1 regulates heme oxygenase-1 [52] [53], senses oxidative DNA damage, and is stimulated by replication protein A to unwind the damaged DNA substrate in a strand-specific manner [54]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cited By (since 1996):4, Export Date: 18 October 2014
Show more

Preview

Download
2 Downloads
Available from